Studies of the late effects of drug therapy are conducted, with special emphasis on the carcinogenic potential of drugs used in a therapeutic setting. Studies of cancer chemotherapeutic agents are a logical extension to the Branch's activities involving second cancer following radiation for a first primary, since many cancer patients are exposed to both treatment modalities. Occasionally, opportunities arise to study other drugs of special interest unrelated to treatment. Sources of populations have included cancer patients reported to population-based cancer registries (particularly the Surveillance, Epidemiologic, and End Results program), randomized clinical trials, and persons treated at major institutions. Additional details on collaborative projects can be found in Project No. Z01CP04412-16 EEB, "Carcinogenic Effects of Therapeutic Drugs" and Project No. Z01CP04410-16 EEB, "Studies of Persons at High Risk of Cancer." Alkylating agents given for breast cancer were linked to significantly high risks of acute leukemia. Melphalan was found to be a potent leukemogen, and to a lesser extent cyclophosphamide. Systemic drug therapy combined with radiation treatment appeared to enhance the risk of leukemia. In contrast, chemotherapy for chronic lymphocytic leukemia was not associated with an excess of second cancer. Radiation treatments for breast cancer were linked to a slight increase in contralateral breast cancer, apparent only among women under age 45 when exposed. Phenobar- bital was found to significantly reduce bladder cancer risk among epileptics. Children treated for retinoblastoma were found to be at very high risk of dying from a second cancer before reaching the age of 40 years, especially those with bilateral disease. Radiotherapy further increased the risk of second cancers, especially osteosarcomas. Radiotherapy for childhood cancer was linked to a high risk of thyroid cancer. Radioactive iodine in the treatment of thyroid cancer appeared unrelated to the risk of second cancers.